Anticoagulation Therapy

Question 1

Key Risk factor increasing the risk of developing VTE

Answer 1

♢ Pregnancy (hyper coagulable state).
♢ Long hospital stay.

♢ Virchow’s Triad: Venous stasis, Vascular injury, Hyper coagulability.
♢ Age (>45)
♢ CHF (stasis due to poor blood flow)

Question 2

VTE prophylaxis

Answer 2

♧ Graduated elastic compression stockings
♧ UFH
♧ LMWH (<15 mL/min avoid)

Question 3

Contraindication for thromboprophylaxis

Answer 3

Bleeds (GI etc), already on anticoagulant, previous HIT reaction.

Question 4

What causes PE?

Answer 4

DVT occurs where a thrombi is being formed and then extended and then emboli breaks off from the thrombi enters into the right chamber of the heart entering the pulmonary circulation precipitating PE.

Question 5

What are the signs of PE.

Answer 5

SOB, chest pain, hemoptysis

Question 6

How do you manage a PE or DVT.

Answer 6

Offer apixaban or rivaroxban (apixaban is preferential) and if either are unsuitable enoxaparin for at least 5 days followed bu dabigatran or edoxaban.

Question 7

How long do offer anticoagulant post-PE or DVT.

Answer 7

AT LEAST 3 MONTHS.

Question 8

Why are anticoagulants indicated in AF as prophylaxis?

Answer 8

The disturbed blood flow due to irregular heart beat (rhythm) and rate allows for blood to pool in the valves of appendageal (commonly left appendageal).
The thrombus can break off and embolise entering the common carotid then brain vasculature leading stroke (or low vasculature resulting in lower limb thrombosis). Six fold increased risk of stroking.

Question 9

Aspirin prevention is recommended in stroke prevention.
True
False

Answer 9

False aspiring only reduces stroke risk by 20%= not effective prevention in primary setting.

Question 10

How is anticoagulant initiated in AF.

Answer 10

Question 11

When do initiate patient with AF on anticoagulation therapy.

Answer 11

♥ CHADVASc score (1) in males and (2) in females.
♥ Risk of stroke is greater than risk of bleeding.
♥ Offer DOAC if patient is unable to take warfarin or unwilling.
♥ Discuss stroke risk reduction, risk of treatment and adherence.

Question 12

What anticoagulant would you use for AF

Answer 12

DOACs.

Question 13

Second line agent if anticoagulation is contraindicated in AF patient

Question 14

Indication for heparin

Answer 14

Treatment of PE, DVT.
Thrombophylaxis in hospital stay patients, pregnancy and surgical patients.

Question 15

Mechanism of action heparin

Answer 15

Inhibit serine protease factors XIIa, XIa, Xa, IXa and thrombin:
1. Directly
2. Potentiation of the plasma serine- protease inhibitor anti-thrombin III.

Question 16

Adverse effects: UFH and LMWH

Answer 16

Bleeding
Osteoporosis
Hyperkalaemia
Heparin induced thrombocytopenia.

Question 17

Antidote for UFH and LMWH

Answer 17

Protamine sulfate (PS),

Question 18

When is LMWH contraindicated?

Answer 18

Manufacturer advises avoid if creatinine clearance less than 15mL/minute.

Question 19

What are the two types of Heparin induced thrombocytopenia. Which one is of importance and fatal.

Answer 19

Type 1: mild thrombocytopenia resolves from day 1-4 were platelet count is less than 150
Type 2: Fatal occurs 5-15 days after therapy has been initiated.

Question 20

Monitoring for heparin

Answer 20

APTT initially then after 6 hours and then adjust according to the result.

Question 21

In renal impairment when would you not use Enoxaparin

Answer 21

CrCl <15

Question 22

Which drugs from the list doesn’t inhibit Factor Xa
a. Apixaban
b. Rivaroxaban
c. Edoxaban
d. Dabigatran

Answer 22

D- inhibits thrombin.

Question 23

Which DOAC doesn’t need LMWH to be used as bridge?
Apixaban
Rivaroxaban
Edoxaban
Dabigatran

Answer 23

(a) Rivaroxaban and (b) Apixaban.

Question 24

Pharmacokinetics in terms of clearance Dabigatran

Answer 24

80% renally excreted.

Question 25

Pharmacokinetics: Rivaroxaban

Answer 25

65% metabolized in the liver. 35% renally cleared. Substrate P-gp and CYP3A4.

Question 26

Pharmacokinetics: Apixaban

Answer 26

73% metabolized by liver Less substrate for CYP3A4. Substrate P-gp

Question 27

Which ones are pharmacodynamic interaction with DOACs
NSAIDS + DOAC
Antiplatelets +DOAC
Itraconazole + DOAC
Carbamazepine + DOACs
SSRIs + DOACs

Answer 27

NSAIDS + DOAC

SSRIs + DOACs

Antiplatelets +DOAC

Question 28

Why are DOACs not used in mechanical valves?

Answer 28

Warfarin has greater superiority in mechanical valve setting according to the RE-ALIGN study: 8 valve Tx had strokes and 4 suffered valve thrombosis when treated with DOACs.

Question 29

Adverse effects DOACS

Answer 29

Anaemia; haemorrhage; nausea;

Question 30

Anticoagulant dissolve clots
True
False

Answer 30

False they only prevent thrombus formation and extension.

Question 31

When would DOAC be contraindicated in patient.

Answer 31

Severe interactions-we would have to switch warfarin
CrCl <30: Dabigatran
CrCl<15: other DOACs

Question 32

Non-oral Oral coagulants MAO

Answer 32

Fondaparinux Selectively binds to antithrombin III, thereby potentiating the innate neutralization of activated factor X (Factor Xa) by antithrombin

Question 33

Alteplase MAO

Answer 33

Converts plasminogen to the proteolytic enzyme plasmin, which lyses fibrin as well as fibrinogen.

Question 34

Select the best option for each scenario provided.
a. Enoxaparin
b. UFH
c. Apixaban
d. Dabigatran
e. Fondaparinux sodium
f. Warfarin
1. A 95-year-old female, weighing 45 kg, with CHADS2 score of 5. She tried warfarin in the past but discontinued due to difficulty with INR monitoring. She has an estimated creatinine clearance of 30 mL/min. What anticoagulant should be prescribed for this patient.

2. A 45-year old patient has creatinine clearance of 13 mL/min, which pharmacological prophylaxis is best suited for him while he stays in hospital.
3. A 60-year-old hypertensive male, who was commenced on a direct-XA inhibitor in the past, as stroke prophylaxis in AF, has developed a troublesome rash and requires an alternative agent. He is needle phobic.
4. Patient has previous HIT on anticoagulant therapy. It was type 1 HIT.
5. 60-year-old patient with mechanical ball in cage valve. What agent do you give.
6. 40-year-old male with CHADVASc score of 3 who has history of non-compliance.

Answer 34

1. (c) Apixaban has less renal involvement and is generally safe at eGRF at 30 mL/min but anything less than 15 mL/min=avoid.
2. (b) UFH. Avoid LMWH in eGFR less than <15 mL/min.
3. (d) Dabigatran is factor IIa inhibitor not Xa inhibitor.
4. (a) LMWH has less HIT occurrence associated.
5. (f) Warfarin is always indicated for valvular disease with mechanical valve= more efficacious.
6. (c) Apixaban is first line ALWAYS

Question 35

Which ONE is NOT a common adverse effect of Warfarin
(a) Teratogenic
(b) Alopecia
(c) Epistaxis
(d) Diarrhoea

Answer 35

(d)

Question 36

Select the best option for each scenario provided.
a. Enoxaparin
b. UFH
c. Apixaban
d. Edoxaban
e. Fondaparinux sodium
f. Warfarin

1. Patient is currently on LMWH and want start and anticoagulant and stop warfarin during this transition. LMWH is still desired to be continued during the transition. What agent would you give.
2. 90-year-old patient with eGRF of 15 mL to be started on venous thromboprphylaxis as outpatient. Which agent is appropriate.

Answer 36

1. (d) Edoxaban
2. (f) Warfarin: less renal involvement than the DOACs (renal function less than <15 mL/min is avoided with DOACs).

Question 37

What is the renal clearance percentage of: Dabigatran, Rivaroxaban, Apixaban, Edoxaban.

Answer 37

Rivaroxaban: ~35%
Apixaban: ~27%
Dabigatran: ~80%

Question 38

Caution with dose adjustment of apixaban

Answer 38

When used for prophylaxis of stroke and systemic embolism in non-valvular atrial fibrillation, manufacturer advises reduce dose to 2.5mg twice daily if serum-creatinine 133micromol/litre and over is associated with age 80 years and over or body-weight 60kg or less; reduce dose to 2.5mg twice daily if creatinine clearance 15–29mL/minute.